Raltegravir not only has a unique mechanism of action, but may also have other unique
effects on suppression of viral replication, viral reservoir, and immune reconstitution in
blood and other important compartments. This may in part be due to the pharmacokinetics of
Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug
in this study, with both drugs being used as part of a three-drug regimen with tenofovir and
emtricitabine.
The primary objectives are to determine differences in the effects of 2 anti-retroviral
regimens, Raltegravir + Truvada versus Atripla, with respect to:
1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ
hybridization).
2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine
profiles.
The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut
tissue; relative tissue/compartment penetration compared to Efavirenz.

The following local sites: Mt. Sinai, Rush University Medical Center, Stroger Hospital,
University of Chicago and University of Illinois will work together to enroll 10 eligible
women meeting all eligibility criteria (5 per study arm) over a one year time period. These
10 women will be randomized 1: 1 to receive either TDF/FTC + Raltegravir or TDF/FTC +
Efavirenz (Atripla). There will be 2 baseline evaluations prior to initiation of study
therapy. Subjects will be followed for 48 weeks after initiation of study treatment.

Eligibility

Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Female.

Criteria:

Inclusion Criteria:
1. Eligible subjects will be antiretroviral naïve (< 7 days of HAART at any time prior
to entry) with plasma HIV-1 RNA > 50,000 copies/mL (obtained within 90 days prior to
study entry by any laboratory that has a CLIA certification or its equivalent) and
moderate immune suppression within 90 days prior to study entry.
2. HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western
blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1
RNA, or a second antibody test by a method other than ELISA is acceptable as an
alternative confirmatory test. Alternatively, if a licensed ELISA is not available,
two HIV-1 RNA values >2000 copies/mL at least 24 hours apart performed by any
laboratory that has CLIA certification or its equivalent may be used to document
infection.
3. Female sex, Age > 18 and < 60 years, Pre-menopausal.
4. Screening CD4+ T-cell count between 200-350 cells/mm3 obtained within 90 days prior
to study entry by any laboratory that has a CLIA certification or its equivalent.
5. The absence of exclusionary resistance mutations on a genotypic resistance assay
(absence of exclusionary NRTI or NNRTI resistance mutations by genotype testing)
6. Antiretroviral (ARV) drug-naïve (defined as 7 days of ARV treatment at any time prior
to entry).
7. Laboratory values obtained within 45 days prior to study entry:

- Female candidates of reproductive potential is defined as women who have had

regular menses over the preceding 24 months
9. Contraception requirements for women who have not undergone surgical sterilization
(e. g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
10. Female candidates of reproductive potential, who are participating in sexual activity
that could lead to pregnancy, must agree to the following:

- If the regimen does not include EFV, they must agree to use at least one

reliable method of contraception while receiving the protocol-specified drugs
and for 6 weeks after stopping the medications.

- If the regimen includes EFV, they must agree to use two reliable methods of

contraception: a barrier method of contraception (e. g., condoms, diaphragm, or
cervical cap with or without spermicide) together with another reliable form of
contraceptive (e. g., a second barrier method, an IUD, or a hormone-based
contraceptive) while receiving EFV and for 6 weeks after stopping EFV.
Exclusion Criteria:
1. Menopausal (may affect quantity of genital tract secretions) or any serious illness
that requires treatment and/or hospitalization until the patient completes therapy
2. Any active infection, including co-infection with hepatitis B or C
3. Any neoplasm
4. Immunosuppressive therapy
5. Requirement for any medications that are prohibited by any of the study treatments
6. Significant liver or renal dysfunction
7. Baseline resistance to any of the study drugs by genotypic testing